It has been determined by us and others that several of the parvoviruses interfere with viral oncogenesis both in vivo and in vitro. The possible role of these ubiquitous agents in cancer resistance has encouraged us to study the phenomenon in detail. We hope to define the spectrum of interference between certain parvoviruses, in particular H-1 virus originally isolated from human tissue, and various viruses which are considered relevant to human malignancy. The biological interplay between H-1 virus and these transforming viruses, some of which act as "helpers," will be explored in productive and nonproductive host cell infections. The molecular basis of the interference with viral transformation, and "helper" virus replication will be sought through an understanding of the molecular biology of H-1 replication. Our recent isolation of conditional lethal mutants of H-1 virus will be an important tool for this. We will seek confirmation of the observation that the transformed phenotype of human cells in vitro is permissive for H-1 replication while the normal phenotype is not. The simplicity and biochemical dependence of H-1 virus on host cell replicative machinery has proven to be more specific that at first realized; this makes the virus a valuable tool for probing many aspects of host cell function. An important aspect of parvovirus biology appears to be latency, and tissue culture and animal models for this will be examined for the mechanism of this phenomenon. BIBLIOGRAPHIC REFERENCES: Rhode, S. L. III. Replication Process of the Parvovirus H-l. VI. Characterization of a Replication Terminus of H-l Replicative-form DNA. J. Virol. 21:694-712, 1977. Toolan, H. W. and Ellem, K. A. O. Parvoviridae. In CRC Handbook Series in Clinical Laboratory Science, Virology and Rickettsiology section, published by CRC Press, Cleveland, OH. G. D. Hsiung and R. H. Green, eds. 1977. in press.